Adults with proximal muscle weakness, elevated creatine kinase (CK) levels, features of myopathy on electromyography (EMG), and evidence of muscle edema on magnetic resonance imaging (MRI) have a broad differential diagnosis that includes autoimmune myopathies, toxic myopathies, paraneoplastic myopathies, and muscular dystrophies. Myopathy is a frequent adverse side-effect that occurs in subjects administered statins to lower their cholesterol. The muscle pain experienced by these patients is sometimes severe enough to warrant termination of statin therapy. Distinguishing between immune-mediated myopathies and other etiologies is crucial, because only autoimmune muscle diseases routinely respond to immunosuppressive therapy.
In many cases, distinctive clinical features and/or a muscle biopsy can provide a definitive diagnosis. For example, perifascicular atrophy is pathognomonic for dermatomyositis (DM) even in the absence of rash; vacuolar myopathy in a patient treated with colchicine strongly suggests a toxic myopathy, and reduced dystrophin staining in the muscle of a young man with calf hypertrophy is diagnostic for a dystrophinopathy.
However, in a substantial number of cases, muscle biopsy specimens show degenerating and necrotic muscle fibers in the absence of disease-specific features. In these instances, the presence of myositis-specific autoantibodies (MSAs) may identify the disorder as belonging to the family of autoimmune myopathies. For example, patients with antibodies directed against the signal recognition particle (SRP) typically have a severe necrotizing myopathy that is responsive only to very aggressive immunosuppression. Unfortunately, clinical evaluation and currently available diagnostic tests do not always provide a definitive diagnosis, and it may not be possible to determine whether a necrotizing myopathy is immune mediated. This uncertainty can lead to undertreatment of autoimmune myopathies or inappropriate immunosuppression in patients who do not have an immune-mediated disease. In sum, current clinical methods are inadequate to diagnose specific muscle diseases in patients experiencing myopathies and improved methods are urgently required.